Leadership roles and initiatives for diversity and inclusion in academic anesthesiology departments.

A cultural change in medicine has placed a renewed focus on the importance of a diverse and inclusive healthcare workforce. The methods employed by anesthesiology departments in pursuit of diversity and inclusion needs to be examined. OBJECTIVE: This study's objective was to assess the frequency of established leadership infrastructures and initiatives that promote diversity and inclusion within academic anesthesiology departments. DESIGN: This was a cross-sectional survey study. The authors emailed an electronic survey to 98 academic anesthesiology departments to assess leadership roles, dissemination platforms and initiatives used to support diversity and inclusion. SETTING: Academic anesthesiology department in the United States with at least 60 residents. MAIN OUTCOME AND MEASURES: The measure tested was the existence and quantification of leadership roles and initiatives directed at diversity and inclusion efforts at academic anesthesiology departments. RESULTS: The survey response rate was 49.4% (95% CI 39.3-59.6%). While 62.5% (95% CI 47.0-75.8%) of respondents reported having faculty members with a diversity and inclusion role, only 27.5% (95% CI 16.1-42.8%) reported a clearly defined leadership role such as vice-chair or committee chair. Seventy percent of respondents reported initiatives geared towards diversity using multiple platforms to showcase these initiatives. CONCLUSIONS: Based on these survey results, many anesthesia departments have developed initiatives to promote their departmental diversity. However, only a minority have established clearly defined leadership roles, which may be critical to enhance departmental success in promoting diversity and inclusion.

Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.

Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.

Determining the efficacy of 27 commercially available disinfectants against human noroviruses.

BACKGROUND: Recently, monoclonal-antibody-conjugated immunomagnetic separation (IMS) procedure combined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) has been used for quantifying non-cultivated human noroviruses (HuNoVs). METHODS: We examined the efficacy of 27 commercially available disinfectants and a prototype against GII.4 strain HuNoV through the IMS/qRT-PCR assay. RESULTS: The average log reduction in viral titer in vitro varied among the disinfectants. The prototype was the most effective with an average log reduction of 6.86 log. CONCLUSIONS: The IMS/RT-qPCR assay is an effective method to evaluate the activities of disinfectants against GII.4 HuNoV in vitro. Further work is needed to enhance the virucidal activity of the prototype disinfectant against more resistant HuNoV strains.

The long-lasting post-stimulation inhibitory effects of bladder activity induced by posterior tibial nerve stimulation in unanesthetized rats.

Tibial nerve stimulation (TNS) is one of the neuromodulation methods used to treat an overactive bladder (OAB). However, the treatment mechanism is not accurately understood owing to significant differences in the results obtained from animal and clinical studies. Thus, this study was aimed to confirm the response of bladder activity to the different stimulation frequencies and to observe the duration of prolonged post-stimulation inhibitory effects following TNS. This study used unanesthetized rats to provide a closer approximation of the clinical setting and evaluated the changes in bladder activity in response to 30 min of TNS at different frequencies. Moreover, we observed the long-term changes of post-stimulation inhibitory effects. Our results showed that bladder response was immediately inhibited after 30 min of 10 Hz TNS, whereas it was excited at 50 Hz TNS. We also used the implantable stimulator to observe a change in duration of the prolonged post-stimulation inhibitory effects of the TNS and found large discrepancies in the time that the inhibitory effect lasted after stimulation between individual animals. This study provides important evidence that can be used to understand the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS as well as the long-lasting prolonged post-stimulation effect.

Bacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling.

Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.

Development of a real-time loop-mediated isothermal amplification method for the detection of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80-100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS.

Incidence and seasonality of respiratory viruses causing acute respiratory infections in the Northern United Arab Emirates.

BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)-related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT-PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak-to-low ratio for FLU was 2.26 (95% confidence interval: 1.52-3.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi-seasonal pattern in the UAE.

MicroRNA miR-223 as regulator of innate immunity.

MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively. MiR-223 contributes to myeloid differentiation by enhancing granulopoiesis while inhibiting macrophage differentiation. Uncontrolled myeloid activation has detrimental consequences in inflammatory disease. MiR-223 serves as a negative feedback mechanism controlling excessive innate immune responses in the maintenance of myeloid cell homeostasis. This review summarizes several topics covering the function of miR-223 in myeloid differentiation, neutrophil and macrophage functions, as well as in inflammatory diseases including acute respiratory distress syndrome and inflammatory bowel disease. In addition, nonmyeloid functions of miR-223 are also discussed in this review. Therapeutic enhancement of miR-223 to dampen inflammatory targets is also highlighted as potential treatment to control excessive innate immune responses during mucosal inflammation.

Precise Determination of the Temperature Gradients in Laser-irradiated Ultrathin Magnetic Layers for the Analysis of Thermal Spin Current.

We investigated the temperature distribution induced by laser irradiation of ultrathin magnetic films by applying a finite element method (FEM) to the finite difference time domain (FDTD) representation for the analysis of thermal induced spin currents. The dependency of the thermal gradient (∇T) of ultrathin magnetic films on material parameters, including the reflectivity and absorption coefficient were evaluated by examining optical effects, which indicates that reflectance (R) and the apparent absorption coefficient (α*) play important roles in the calculation of ∇T for ultrathin layers. The experimental and calculated values of R and α* for the ultrathin magnetic layers irradiated by laser-driven heat sources estimated using the combined FDTD and FEM method are in good agreement for the amorphous CoFeB and crystalline Co layers of thicknesses ranging from 3~20 nm. Our results demonstrate that the optical parameters are crucial for the estimation of the temperature gradient induced by laser illumination for the study of thermally generated spin currents and related phenomena.

Author Correction: Metabolic gatekeeper function of B-lymphoid transcription factors.

In Fig. 3c of this Letter, the the effects of CRISPR-Cas9-mediated deletion of NR3C1, TXNIP and CNR2 in patient-derived B-lineage leukaemia cells were shown. For curves depicting NR3C1 (left graph), data s for TXNIP (middle graph) were inadvertently plotted. This figure has been corrected online, and the original Fig. 3c is shown as Supplementary Information to this Amendment for transparency. The error does not affect the conclusions of the Letter. In addition, Source Data files have been added for the Figs. 1-4 and Extended Data Figs. 1-10 of the original Letter.

Flexible h-BN foam sheets for multifunctional electronic packaging materials with ultrahigh thermostability.

Recently developed electronic packaging materials based on low dimensional materials such as carbon nanotubes, graphene, and hexagonal boron nitride (h-BN) exhibit advantageous electrical, thermal, and mechanical properties for protecting electronic devices as well as dissipating heat flux from highly integrated circuits or high power electronic devices. Their thermal transport is mainly achieved by precise control of the nanostructure for nano-fillers to form the thermally conductive pathway. However, due to the viscoelastic behaviors of host polymeric materials, their phase or structural stability is significantly reduced by enhanced molecular motion at high temperature, resulting in poor thermal transport and mechanical strength. Here, we introduce flexible and robust h-BN foam sheets with a three-dimensional network structure, which exhibit much enhanced thermostability at high temperature. Furthermore, the additional infiltration of Fe3O4 nanoparticles into those structures results in relatively high electromagnetic absorbing performance. The combination of thermostability and mechanical strength based on the h-BN foam sheets provides novel opportunities for multifunctional thermally conductive materials in coatings and films without severely compromising auxiliary characteristics such as mechanical strength and thermal stability.

Detecting Bladder Biomarkers for Closed-Loop Neuromodulation: A Technological Review.

Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient's state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction.

Biosynthesis of Oligomeric Anthocyanins from Grape Skin Extracts.

We synthesized oligomeric anthocyanins from grape skin-derived monomeric anthocyanins such as anthocyanidin and proanthocyanidin by a fermentation technique using Aspergillus niger, crude enzymes and glucosidase. The biosyntheses of the oligomeric anthocyanins carried out by the conventional method using Aspergillus niger and crude enzymes were confirmed by ESI-MS. The molecular weight of the synthesized anthocyanin oligomers was determined using MALDI-MS. The yield of anthocyanin oligomers using crude enzymes was higher than that of the synthesis using Aspergillus fermentation. Several studies have been demonstrated that oligomeric anthocyanins have higher antioxidant activity than monomeric anthocyanins. Fermentation-based synthesis of oligomeric anthocyanins is an alternative way of producing useful anthocyanins that could support the food industry.

Metabolic gatekeeper function of B-lymphoid transcription factors.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.

The Significant Influence of Bacterial Reaction on Physico-Chemical Property Changes of Biodegradable Natural and Synthetic Polymers Using Escherichia coli.

Escherichia coli (E. coli) was used to activate hydrolysis reaction along with biodegradation in natural and synthetic fibers to identify possibilities as alternative substitutes for textile wastes using chemical solutions and enzymes. To confirm the reaction between the bacterial infections of E. coli and the excessively abundant interstitial spaces of the fibers, various types of natural and synthetic fibers such as cotton, wool, polyethylene terephalate (PET), polyadmide (PA), polyethylene (PE), and polypropylene (PP) were used to confirm the physico-chemical reactions. Tensile strength analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle analysis were used to determine the physico-chemical property changes of the fiber by the bacteria. When biofilm was formed on the fiber surface, various physical changes such as the following were observed: (i) in the analysis of tensile strength, all except PA and PP were decreased and a decrease in cotton fibers was noticeable (ii) depending on the type of fibers, the degree of roughness was different, but generally the surface became rough. In this study, the change of roughness was the most severe on the cotton fiber surface and the change of PET and PA fiber was relatively small. It was found that the intensity peak of oxygen was increased, except for the in cases of PA and PP, through the change of chemical properties by XPS analysis. Changes in topographical properties on the surface through contact angle analysis were stronger in hydrophilic properties, and in the case of cotton, completely hydrophilic surfaces were formed. Through this study, PA and PP fibers, which are Olefin fibers, were theoretically free of physicochemical and topographical changes since there were no functional groups that could trigger the hydrolysis reaction.

In Vitro and In Vivo Anti-Allergic and Anti-Inflammatory Effects of eBV, a Newly Developed Derivative of Bee Venom, through Modulation of IRF3 Signaling Pathway in a Carrageenan-Induced Edema Model.

BACKGROUND: Bee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action. METHODS: The anti-inflammatory potential of eBV was assessed in vivo using a carrageenan-induced paw edema model. To further investigate the mechanism by which eBV exerts anti-allergic and anti-inflammatory effects, compound 48/80-stimulated RBL-2H3 cells and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were studied in vitro. RESULTS: Release of ß-hexosaminidase and histamine was increased by eBV in a dose-dependent manner, but these levels were lower in eBV compared to original BV at the same concentration. In addition, eBV suppressed compound 48/80-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in RBL-2H3 cells. eBV was also shown to suppress nitric oxide (NO) production by down-regulating mRNA expression and subsequent protein expression of inflammatory mediators in LPS-induced RAW 264.7 cells. Phosphorylation of activators and signal transducers of transcription 1/interferon regulatory factor 3 (STAT1/IRF3) was attenuated by eBV treatment. eBV significantly inhibited carrageenan-induced acute edema in vivo. Serum levels of prostaglandin E2 (PGE2), TNF-α, and IL-1ß were also down-regulated by eBV. CONCLUSIONS: These results demonstrate that eBV inhibits allergic and inflammatory response by reducing inflammatory mediator production via regulation of the STAT1/IRF3 signaling pathway, suggesting that eBV is a feasible candidate for regulation of allergic-inflammatory response in complementary and alternative medicine.

Safety of essential bee venom pharmacopuncture as assessed in a randomized controlled double-blind trial.

ETHNOPHARMACOLOGICAL RELEVANCE: While bee venom (BV) pharmacopuncture use is common in Asia, frequent occurrence of allergic reactions during the treatment process is burdensome for both practitioner and patient. AIM OF THE STUDY: This study compared efficacy and safety in isolated and purified essential BV (eBV) pharmacopuncture filtered for phospholipase A2 (PLA2) and histamine sections, and original BV to the aim of promoting safe BV pharmacopuncture use. MATERIALS AND METHODS: In in vitro, we examined the effect of BV and eBV on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and clinically, 20 healthy adults aged 20-40 years were randomly allocated and administered eBV 0.2mL and BV pharmacopuncture 0.2mL on left and right forearm, respectively, and physician, participant, and outcome assessor were blinded to treatment allocation. Local pain, swelling, itching, redness, wheals, and adverse reactions were recorded by timepoint. RESULTS: eBV and BV exhibited similar inhibitory effects on NO production. Also, in comparison between eBV and BV pharmacopuncture administration areas on each forearm, eBV displayed significantly lower local pain at 24h post-administration (P=0.0062), and less swelling at 30min (P=0.0198), 2 (P=0.0028), 24 (P=0.0068), and 48h post-administration (P=0.0253). eBV also showed significantly less itching at 24 (P=0.0119), 48 (P=0.0082), and 96h (P=0.0141), while redness was significantly less at 30min (P=0.0090), 6 (P=0.0005), and 24h (P<0.0001). Time-by-treatment interactions were statistically significant for itching and redness (P<0.001, and P<0.001, respectively), and all original BV pharmacopuncture administered regions showed a tendency toward more severe itching and redness in later measurements. CONCLUSIONS: eBV and BV displayed comparable anti-inflammatory effects, and eBV pharmacopuncture presented less local allergic reactions.

Prognostic value and their clinical implication of 89-gene signature in glioma.

Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

Complete genome sequencing of a recombinant strain between human astrovirus antigen types 2 and 8 isolated from South Korea.

Human astroviruses (HAstVs) occur worldwide and are known to the causative agents of diarrhea in infants and elderly patients with immune dysfunction. This study aimed to identify recombinant HAstV strains and characterize rare genotypes. The full-length genome of a recombinant HAstV strain isolated from the stool sample of a patient with acute gastroenteritis from South Korea was amplified using three pairs of previously designed primers and seven newly designed primers. The recombinant HAstV was 6757-bp long and contained three sequential open reading frames (ORFs), designated as ORF1a (2781 bp), ORF1b (1548 bp), and ORF2 (2349 bp). Our findings suggested that a recombination event had occurred between ORF1b and ORF2 of the isolated strain, with a recombination breakpoint at 4081 bp. To our knowledge, this is the first study to reveal the complete nucleotide sequence of a recombinant HAstV strain from South Korea. Our study findings might be useful for identifying other recombinant HAstV strains and for developing vaccines against this pathogenic virus.